This proposal describes a research program in basic physiology aimed at elucidating the mechanism of hepatic transport and the pathogenesis of cholestasis. The experiments are designed to pursue the following objectives: 1) assemble a comprehensive kinetic description of the transport kinetics of representative organic solutes during experimental choleresis and cholestasis, 2) explore the kinetics, specificity, and functional importance of the process by which the liver efficiently removes solutes that are extensively bound to serum albumin, and 3) construct and analyze a mathematical model of canalicular bile formation that can provide new insights into the determinants of the translobular concentration and flow profiles in the canaliculi. The experimental preparations include isolated perfused rat livers, perfused segments of rat terminal ileum, and isolated rat hepatocytes. The analytical methods rely heavily on the biomathematics of compartmental analysis.